Published Surgical Results

• Electrical Stimulation of the Subthalamic Nucleus in Advanced Parkinson's Disease, Limousin P, Krack P, Pollak P, Benazzouz A, et al.: N Engl J Med 1998; 339: 1105-11
  • In advanced Parkinson's disease (PD) one of the chief problems with levodopa treatment is the 'on-off' phenomenon that results in large fluctuations in motor symptoms as drug levels vary. Animal experiments, in which a Parkinsonian state has been artificially created in monkeys, suggest that electrical stimulation of the subthalamic nucleus may improve motor symptoms in PD. This French study explored this observation further in 24 human subjects.
  • Twenty-four patients with idiopathic advanced PD were selected for bilateral implantation of electrodes in the subthalamic nucleus. All had disabling motor fluctuations despite all adjustments in drug therapy. During 'off' periods they all had severe impairment of activities of daily living whilst during 'on' periods they all suffered from levodopa induced dyskinesias. Mean age was 56 years, with a mean duration of PD of 14 years.
  • Clinical evaluation of the patients before surgery was performed using the Unified Parkinson's Disease Rating Scale (UPDRS). Subjects were assessed during both 'off' and 'on' periods.
  • Surgery was performed under local anesthetic to insert bilateral electrodes into the subthalamic nucleus. The nucleus was located using MRI and electrophysiologic recordings of characteristic activity. The electrodes were connected to a pulse generator that was placed subcutaneously in the upper chest (in a similar fashion to a cardiac pacemaker). The pulse generator could be programmed by telemetry, it was adjusted by neurologists at each follow-up visit.
  • Subjects have been followed for up to 36 months. The primary outcome measure was change in parts II (activities of daily living) and III (motor examination) of the UPDRS. They were reassessed both during 'on' and 'off' periods with the pulse generator switched both on and off. The patients were unaware during assessments as to the generator status.
  • After one year the patients' UPDRS scores for both parts II and III, during stimulation, had improved by 60% during 'off' periods. In 'on' periods the UPDRS scores improved 10%. The mean dose of dopaminergic drugs used was reduced by half, with a concomitant decrease in dyskinesia during the 'on' periods. One patient stopped levodopa treatment altogether.
  • The procedure was not without risk. One patient developed an 8 cm intracranial hematoma during the neurosurgery leading to severe paralysis and aphasia. One patient developed an subcutaneous infection near the generator site, it had to be removed for six months. Five patients had increased difficulty opening their eyes post-surgery; the mechanism of this adverse effect is unclear.
    • In conclusion, chronic bilateral electrical stimulation of the subthalamic nucleus produced some large improvements in motor fluctuations in subjects with advanced PD and allowed a reduction in medication. There were some adverse events associated with the treatment, implying that it should be reserved for severely disabled patients.

The results from centers abroad have been very encouraging and at times dramatic. In these studies using chronic high frequency bilateral STN stimulation, the patients had improvements in the total motor score of 60% with subscore improvements in bradykinesia, rigidity, tremor, gait and postural instability while off medications. Additionally, there was a reduction in dyskinesias of greater than 70% and reduction of dopaminergic drug dose by more than 50%.

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